A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01364389
• Collaborator: (none)
• Enrollment: 16
• Locations: 6
• Arms: 3
• Actual Duration (Months): 23.5
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. The protocol will seek to enroll a total of 30 patients, who will be randomized to the 3 arms at a ratio of 1:1:1.

Patients will have a maximum screening period of 7 days with randomization at D1 for a dosing period of 15 days followed by a follow up-period of 154 days, or 4 months (112 days) after their last biologic dose, whichever is greater, and followed by unblinded re-dosing in the case of a disease flare.

Condition or Disease	Intervention/Treatment	Phase
Polymyalgia Rheumatica; Inflammatory Diseases	Drug: AIN457; Drug: ACZ885; Drug: Prednisone; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 2-week Single-blind, Randomized, 3-arm Proof of Concept Study of the Effects of AIN457 (Anti-IL17 Antibody), ACZ885 (Canakinumab, Anti-IL1b Antibody), or Corticosteroids in Patients With Polymyalgia Rheumatica, Followed by an Open Label Phase to Assess Safety and Long Term Efficacy
• Actual Study Start Date: Feb 14, 2011
• Actual Primary Completion Date: Jan 29, 2013
• Actual Study Completion Date: Jan 29, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ACZ885 On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	Drug: AIN457; 3 mg/kg; Drug: Placebo; Matching placebo to AIN457, ACZ885 and prednisone
Experimental: AIN457 On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	Drug: ACZ885; 3 mg/kg; Other Names: canakinumab ; Drug: Placebo; Matching placebo to AIN457, ACZ885 and prednisone
Other: Prednisone On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.	Drug: Prednisone; 20 mg; Drug: Placebo; Matching placebo to AIN457, ACZ885 and prednisone

Outcome Measures

Primary Outcome Measures

1. Polymyalgia Rheumatica Activity Score (PMR-AS) [Baseline, Day 15]

   The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.

Secondary Outcome Measures

1. Time to Partial Clinical Response [Day 15]

   The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had: >50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.

2. Time to Complete Clinical Response [Day 15]

   The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.

3. Time to First Flare [6 months]

   This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44

4. Number of Flares Over a 6 Month Period [6 months]

   This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

5. Mean Steroid Dose Over a 6 Month Period [6 months]

   This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

6. Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths [6 months]

7. Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing. [6 months]

   One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.

8. Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire [6 months]

   The Short Form-36 (SF-36) Questionnaire is a 36-item questionnaire yields an 8-scale health profile as well as summary measures of individual patients.. The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.

9. Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) [baseline and at month 6]

   HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.

10. Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6 [6 months]

    HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.

11. Pharmacokinetics of AIN457 and ACZ885 - Cmax [Day 15]

12. Pharmacokinetics of AIN457 and ACZ885 - Tmax [Day 15]

13. Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast [Day 15]

14. Pharmacokinetics of AIN457 and ACZ885 - CL [Day 15]

15. Pharmacokinetics of AIN457 and ACZ885 - Vz [Day 15]

16. Pharmacokinetics of AIN457 and ACZ885 - T1/2 [Day 15]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must meet all of the following features:

• Patients ≥ 50 and ≤ 85 years

• C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr

• New bilateral shoulder and/or hip pain

• Early morning stiffness ≥ 60 min

• Duration of illness > 1 week

• A negative 5 U purified protein derivative skin test (PPD) skin test (≤ 5 mm induration) at screening

Exclusion Criteria:

• Active infection or current use of antibiotics

• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV)

• Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline

• History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry

• Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis.

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Rochester	Minnesota	United States	55905
2	Novartis Investigative Site	Berlin		Germany	13125
3	Novartis Investigative Site	Reggio Emilia	RE	Italy	42123
4	Novartis Investigative Site	Siena	SI	Italy	53100
5	Novartis Investigative Site	Basildon	Essex	United Kingdom	SS16 5NL
6	Novartis Investigative Site	Westcliff-on-Sea	Essex	United Kingdom	SS0 0RY

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01364389
• Other Study ID Numbers: CPJMR0012201; 2010-019395-73
• First Posted: Jun 2, 2011
• Last Update Posted: Sep 17, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Novartis Pharmaceuticals: Polymyalgia Rheumatica; Inflammatory Disease; Rheumatic Disease
• Additional relevant MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Prednisone

Study Results

Participant Flow

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Period Title: Overall Study
STARTED	5	6	5
Pharmacodynamic (PD) Analysis Set	5	6	4
COMPLETED	3	5	4
NOT COMPLETED	2	1	1

Baseline Characteristics

Arm/Group Title	ACZ885	AIN457	Prednisone	Total
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.	Total of all reporting groups
Overall Participants	5	6	5	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.2 (9.09)	68.8 (8.61)	69.4 (7.89)	68.5 (8.02)
Sex: Female, Male (Count of Participants)
Female	4 80%	2 33.3%	5 100%	11 68.8%
Male	1 20%	4 66.7%	0 0%	5 31.3%

Outcome Measures

1. Primary Outcome

Title	Polymyalgia Rheumatica Activity Score (PMR-AS)
Description	The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) Analysis Set: This set included participants who received at least one dose of study medication and had no major protocol deviation that may impact the PD data.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	3	6	4
Least Squares Mean (Standard Error) [Percent reduction]	64.5 (0.68)	51.7 (0.47)	91.9 (86.2)

2. Secondary Outcome

Title	Time to Partial Clinical Response
Description	The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had: >50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

PD analysis set

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	5	6	4
Number [Percentage of participants]	20.0 400%	16.7 278.3%	75.0 1500%

3. Secondary Outcome

Title	Time to Complete Clinical Response
Description	The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

PD analysis set

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	5	6	4
Number [Percentage of participants]	0.0 0%	0.0 0%	25.0 500%

4. Secondary Outcome

Title	Time to First Flare
Description	This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	0	1	0
Number [Days]	44

5. Secondary Outcome

Title	Number of Flares Over a 6 Month Period
Description	This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	0	1	0
Number [Participant]	1

6. Secondary Outcome

Title	Mean Steroid Dose Over a 6 Month Period
Description	This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	3	4	4
Mean (Standard Deviation) [Number of doses]	276.8 (46.34)	256.7 (27.89)	428.9 (131.44)

7. Secondary Outcome

Title	Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Safety analysis set: This set included all participants who received at least one dose of study medication.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	5	6	5
Adverse Events (serious and non-serious)	3 60%	2 33.3%	5 100%
Serious Adverse Events	0 0%	0 0%	0 0%
Deaths	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.
Description	One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
Description	The Short Form-36 (SF-36) Questionnaire is a 36-item questionnaire yields an 8-scale health profile as well as summary measures of individual patients.. The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	5	6	4
Physical component score at baseline	26.126 (8.1517)	29.009 (4.3115)	27.001 (5.2561)
Physical component score at EOS / Month 6 (n=4,6,2)	44.293 (12.6038)	48.496 (8.2306)	34.544 (7.7632)
Mental component score at baseline	30.490 (11.2875)	35.779 (5.9113)	29.673 (6.1925)
Mental component score at month 6 / EOS (n=4,6,2)	44.668 (20.3716)	54.136 (8.8815)	55.233 (2.8274)

10. Secondary Outcome

Title	Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
Description	HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Time Frame	baseline and at month 6

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	5	6	4
standard disability score at baseline	1.900 (0.6869)	1.646 (0.2896)	2.063 (0.2394)
standard disability score at EOS / Month 6 (n=4,6,3)	0.719 (1.0225)	0.188 (0.3513)	0.958 (0.3819)

11. Secondary Outcome

Title	Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6
Description	HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457	Prednisone
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Measure Participants	4	6	3
Mean (Standard Deviation) [Percentage]	-68.06 (36.781)	-86.83 (25.478)	-54.04 (12.296)

12. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - Cmax
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurement for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	4	3
Mean (Standard Deviation) [microgram/mL]	69.9 (5.58)	46.8 (2.85)

13. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - Tmax
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurement for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	4	3
Median (Full Range) [days]	0.0868	0.107

14. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	3	2
AUCinf (microg/day/mL)	1570 (80)	1260 (134)
AUClast (microg/day/mL)	1560 (74.7)	1200 (132)

15. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - CL
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	3	2
Mean (Standard Deviation) [L/day]	0.171 (0.440)	0.157 (0.0106)

16. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - Vz
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	3	2
Mean (Standard Deviation) [L]	6.49 (1.19)	9.85 (1.29)

17. Secondary Outcome

Title	Pharmacokinetics of AIN457 and ACZ885 - T1/2
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.

Arm/Group Title	ACZ885	AIN457
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.	On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Measure Participants	3	4
Mean (Standard Deviation) [Day]	26.6 (2.38)	40.2 (4.47)

Adverse Events

Time Frame	Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 239 days
Arm/Group Title	ACZ885 3mg/kg		AIN457 3mg/kg		Prednisone 20mg
Arm/Group Description	On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.		On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.		On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
All Cause Mortality
	ACZ885 3mg/kg		AIN457 3mg/kg		Prednisone 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		0/5 (0%)
Serious Adverse Events
	ACZ885 3mg/kg		AIN457 3mg/kg		Prednisone 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	ACZ885 3mg/kg		AIN457 3mg/kg		Prednisone 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		2/6 (33.3%)		5/5 (100%)
Ear and labyrinth disorders
Vertigo	0/5 (0%)		0/6 (0%)		1/5 (20%)
Eye disorders
Eye pain	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/5 (0%)		0/6 (0%)		1/5 (20%)
Dyspepsia	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Gastrooesophageal reflux disease	1/5 (20%)		0/6 (0%)		0/5 (0%)
Oral mucosal blistering	0/5 (0%)		0/6 (0%)		1/5 (20%)
Toothache	1/5 (20%)		0/6 (0%)		0/5 (0%)
Infections and infestations
Bronchitis	0/5 (0%)		0/6 (0%)		1/5 (20%)
Nasopharyngitis	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Sinusitis	1/5 (20%)		0/6 (0%)		0/5 (0%)
Upper respiratory tract infection	1/5 (20%)		0/6 (0%)		1/5 (20%)
Investigations
Blood pressure increased	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Weight increased	0/5 (0%)		0/6 (0%)		1/5 (20%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)		1/6 (16.7%)		1/5 (20%)
Arthritis	0/5 (0%)		0/6 (0%)		1/5 (20%)
Joint swelling	1/5 (20%)		1/6 (16.7%)		0/5 (0%)
Muscle spasms	0/5 (0%)		0/6 (0%)		1/5 (20%)
Seronegative arthritis	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Nervous system disorders
Headache	0/5 (0%)		1/6 (16.7%)		1/5 (20%)
Lethargy	0/5 (0%)		1/6 (16.7%)		0/5 (0%)
Presyncope	0/5 (0%)		0/6 (0%)		1/5 (20%)
Psychiatric disorders
Insomnia	1/5 (20%)		0/6 (0%)		0/5 (0%)
Sleep disorder	0/5 (0%)		1/6 (16.7%)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/5 (20%)		0/6 (0%)		0/5 (0%)

Limitations/Caveats

This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.